2. Academic Validation
  3. PF-PEG@ASIV-EXO Hydrogel Accelerates Diabetic Wound Healing by Ferroptosis Resistance and Promoting Angiogenesis

PF-PEG@ASIV-EXO Hydrogel Accelerates Diabetic Wound Healing by Ferroptosis Resistance and Promoting Angiogenesis

  • ACS Biomater Sci Eng. 2024 Oct 14;10(10):6263-6285. doi: 10.1021/acsbiomaterials.4c00692.
Wu Xiong 1,  Xi Zhang 2,  Jinhui Hu 3,  Xiaoling Zou 4,  Hongyu Huang 5,  Wenjing Qu 4,  Shimin Cai 5,  Chengyu Li 5,  Yang Wei 5,  Xingxing Zhong 5,  Zhaoyang Cai 5,  Zixin Huang 6
Affiliations

Affiliations

  • 1 Department of Burns and Plastic Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China.
  • 2 Clinical Medical School of Hunan University of Chinese Medicine, Hunan Brain Hospital, Changsha 410007, China.
  • 3 Department of Breast Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China.
  • 4 Department of Endocrinology, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, China.
  • 5 College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
  • 6 College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
PMID: 39311841 DOI: 10.1021/acsbiomaterials.4c00692
Abstract

Astragaloside IV (ASIV) promotes the proliferation of key cells, endothelial progenitor cells (EPCs), during the wound healing process, while exosomes and hydrogels are ideal drug delivery carriers. This study aims to explore the mechanism of action of the "ROS-responsive hydrogel-engineered EPCs-targeted exosomes" composite ASIV delivery system (PF-PEG@ASIV-EXO) in diabetic wound healing. Surface markers of EPCs and PF-PEG@ASIV-EXO were detected separately. The degradation rate of PF-PEG@ASIV-EXO was assessed after coculturing with human dermal fibroblasts (HDF), immortalized human epidermal cells (HaCAT), and human EPCs, and the biocompatibility of EPCs and PF-PEG@ASIV-EXO was evaluated through exosome release and uptake. The effects of PF-PEG@ASIV-EXO on the viability, angiogenesis, Ferroptosis, and mitochondria of high-glucose-treated EPCs (HS-EPCs) were investigated. A diabetic wound rat model was established, and the effects of PF-PEG@ASIV-EXO on diabetic wounds were evaluated through HE and Masson staining, as well as levels of VWF, CD31, and Ferroptosis in the skin. EPCs were successfully isolated, and PF-PEG@ASIV-EXO was successfully constructed. PF-PEG@ASIV-EXO exhibited a high degradation rate within EPCs, and both EPCs and PF-PEG@ASIV-EXO showed good biocompatibility. PF-PEG@ASIV-EXO promoted the vitality and angiogenesis of EPCs, inhibited Ferroptosis, and mitigated mitochondrial damage. Following treatment with PF-PEG@ASIV-EXO, the healing of diabetic rat skin accelerated, accompanied by elevated expression of VWF and CD31, and reduced Ferroptosis levels. PF-PEG@ASIV-EXO hydrogel inhibits Ferroptosis, promotes angiogenesis, and thereby accelerates the healing of diabetic wounds.

Keywords

Angiogenesis; Diabetic wound; EPCs; Ferroptosis; PF−PEG@ASIV-EXO.

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